Decreased p44/42 mitogen-activated protein kinase phosphorylation in gender- or hormone-related but not during age-related adrenal gland growth in mice.
Postnatal growth of the mouse adrenal gland shows a characteristic gender-dependent pattern, resulting in an almost 2-fold higher adrenal weight in 11-wk-old female vs. male mice. We demonstrated that the higher weight of the adrenal glands in female mice is due to a significantly (P < 0.05) increased growth rate in female mice and a shorter growth phase of the adrenal glands in male mice (P < 0.05). To address the signaling mechanisms underlying these differential growth patterns, we evaluated the phosphorylation levels of p44/42 and p38 MAPK. In female mice, age-dependent reductions of p38 MAPK phosphorylation were found between wk 3 and 9 (47% reduction; P < 0.05). At the age of 11 wk, the p38 MAPK phosphorylation level in female adrenal glands was about 60% lower than in the male counterparts (P < 0.01). Similarly, the phosphorylation level of p44/42 MAPK was 50% lower in female adrenal glands (P < 0.001). Reduced activation of p44/42 MAPK was also observed after growth stimulation of the adrenal glands in male mice after ACTH treatment (-36%; P < 0.001) or by expression of a GH transgene (-34%; P < 0.001), whereas p38 MAPK, JNK, or PDK1 activation was unaffected. From our findings in three independent mouse models where partial deactivation of p44/42 MAPK was observed under conditions of elevated growth, we suggest a function of p44/42 MAPK for adrenal growth and a role of p44/42 MAPK for the integration of different endocrine stimuli.
Bielohuby
Maximilian
M
Department of Medicine Innenstadt, Division of Endocrine Research, Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität, Munich,Germany.
Sawitzky
Mandy
M
Johnsen
Inga
I
Wittenburg
Dörte
D
Beuschlein
Felix
F
Wolf
Eckhard
E
Hoeflich
Andreas
A
D000311:Adrenal Glands / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000235:genetics; D006728:Hormones / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012727:Sex Characteristics
D006728:Hormones; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3